Effectiveness of Nilotinib in TNBS-Induced Colitis Model of Rats

Introduction and Aim:Inflammatory bowel disease (IBD) is group of diseasewith limited treatment alternatives which immunological, genetic and environmental factorscontributestill unexplainedliterally. The aimof the present study wasto investigate the effects of nilotinib, a tyrosine kinase inhibitor, in Trinitrobenzene sulfonic acid (TNBS) induced colitis model in rats. Method:We included 21 rats with an average weight of 209,43 ± 8,92 gr in the study which was provided by Dokuz Eylul University Medicine Faculty (DEUTF) Experimental Research Laboratory. Rectal saline was administered to healthy control group (Group 1) rats (n:7). No treatment was given to positive control group (Group 2) rats (n:7) after administering TNBS through rectal cannula. Nilotinib 20mg/kg in two separate doses per day were administered by orogastric catheter initiating from same day of TNBS administration to 14thday in treatment group (Group 3) rats (n:7). Their daily weights were recorded for 14 days. At the end of the study the rats were sacrificed. Macroscopic, microscopic scores, apoptotic index, PDGFR alpha and beta scores with immunohistochemistrical method were evaluated between groups. Tissue and serum TNF-alpha levels were detected with ELISA method. Results:There were statistically significant differencesin weights between 1stand 14thday between Group 1 and Group 3, Group 2 and Group 3 andGroup 1 and Group 2 (+8.3 gr and -0.7 gr, P=0.031; -14.0 gr and -0.7 gr, P=0.047; +8.3 gr and -14.0 gr, P=0.008, respectively). While no significant difference for Group 1 vs.Group 3 could be determined for macroscopic pathologic scores, macroscopic scores in the Group 1 and Group 3 were significantly lower than in Group 2 (0 and 1.43±0.65,P=0.014;1.43±0.65 and 0, P=0.009, respectively). Microscopic pathologic scores in Group 1 and Group 3 were similar. There were significant differencesbetween Group 1 and Group 2 with Group 2 and Group 3 in microscopic scores (2.0±0.45 and 7.71±1.48, P=0.034; 7.71±1.48and 2.86±0.53, P=0.030, respectively). PDGFR alpha scores in Group 1 and Group 3 were significantly lower than in Group 2(1.33±0.21 and2.71±0.18, P=0.004; 2.71±0.18 and 1.57±0.3, P=0.014,respectively). Also there were significant differencesbetween Group1 and Group 2 with Group 2 and Group 3 in PDGFR beta scores (1.50±0.22 and 2.57±0.20, P=0.011; 2.57±0.20 and 1.57±0.3,4P=0.025,respectively). Group 1 and Group 3 were found to be similar regardingboth PDGFR alpha and PDGFR beta scores. The significant differences were found in tissue TNF-alpha levels between Group 1 and Group 2 with Group 1 and Group 3 (0.23±0.01 and 0.39±0.06, P=0.002; 0.23±0.01 and 0.40±0.05, P=0.003,respectively). Tissue TNF-alpha levels were similar in Group 2 and 3. All groups were similar in terms of serum TNF-alpha levels and apoptosis. Conclusion: Nilotinib has significanteffects on the weightchangeand macroscopic and microscopic pathological scores in TNBS induced colitis rat model. So, the present study showed that nilotinib induce remarkable and significant mucosal healing. Nilotinib did not have considerable effects on the level of TNF-alpha andapoptotic score; however, nilotinib decreasedPDGFR alpha and beta levels.Key Words:Nilotinib, TNBS, PDGFR, TNF alpha, ra